Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1309657 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Bavachin (BV), a therapeutic phytoestrogen in Fructus Psoraleae (FP), has been used in various diseases. However, the molecular mechanism of BV hepatotoxicity reported by many studies remains unclear. Here, we used single cell RNA sequencing (scRNA-seq) to explore the early cytotoxicity induced by BV in the liver.
2023-08-21 | GSE216336 | GEO
Project description:Epimedii Folium (EF) is widely used in traditional Chinese medicine, yet its hepatotoxic risk is increasingly recognized to be highly context dependent. This study demonstrates that EF induces significant liver injury only under conditions of immune stress, characterized by a pro-inflammatory and metabolically vulnerable hepatic state. Importantly, herb compatibility critically modulates this risk. Co-administration of Psoraleae Fructus (PF) markedly exacerbated EF-induced hepatotoxicity through amplification of inflammatory and cell death–related pathways, whereas Rhizoma Drynariae (RD) partially attenuated liver injury by stabilizing cholesterol and bile acid metabolism and restoring hepatic homeostasis
2026-07-26 | GSE317736 | GEO
Project description:Liver transcriptome of Psoraleae Fructus decoction induced liver damage in mice
| PRJNA767360 | ENA
Project description:Kidney-yang deficiency syndrome (KYDS) is a metabolic disease caused by neuroendocrine disorders often accompanied by abnormal liver function. Psoraleae Fructus (BGZ) is widely used to treat KYDS in China, but it is unclear whether BGZ plays a therapeutic role in regulating liver function. Organ index, ALT, AST, and HE staining were used to evaluate the protective effect of BGZ on KYDS in rats, and transcriptomics and metabolomics were employed to screen for potential biomarkers. The results showed that BGZ treatment significantly decreased the levels of ALT and AST, and ameliorated liver pathological damage in KYDS rats. 92 differentially expressed genes (DEGs) and 20 metabolites were significantly disturbed by BGZ in KYDS rats. Integrated analysis of metabolites and DEGs revealed that neuroactive ligand-receptor interaction, cAMP pathway, calcium signaling pathway, and cytokine-cytokine receptor interaction may be the main mechanism of BGZ treatment, and the key targets of the cAMP pathway were confirmed by ELISA and RT-qPCR. In conclusion, the cAMP pathway may be the partial mechanism by which BGZ exerts protective effects on KYDS, and the study results also lay the foundation for more in-depth mechanistic studies and drug-targeted therapy of KYDS in the future.
2023-12-31 | GSE249348 | GEO
Project description:Psoraleae Fructus can cause liver damage, we study its effect on liver transcription,According to the sequence data, a total 6689 mRNAs were identified. Compared with control group, 1814 differential mRNAs were identified in the SPHD group, including 939 upregulated mRNAs and 875 downregulated mRNAs. Top 20 pathways are shown in the result, including “Metabolic pathways”, “NOD−like receptor signaling pathway”, “PI3K−Akt signaling pathway”, “Drug metabolism − other enzymes”, and “Estrogen signaling pathway”. To understand the functions of differential mRNAs, the target genes of differential mRNAs were predicted and were mapped to terms in the GO database and compared with the background (Figure 5C). The GO has 3 ontologies, which are “biological process”, “cellular component”, and “molecular function”. In the “biological process” part, most genes were related to “immune system process”, “oxidation−reduction process”, and “transport”. In the “cellular component” part, most genes were related to the “ribosomal part”, “mitochondrial part” and “membrane part”. In the “molecular function” part, most genes were related with “structural constituent of ribosome part”, “protein binding ” and “poly(A) RNA binding”.
2024-09-29 | GSE185007 | GEO
Project description:New approach methodologies (NAMs) are advancing the reduction of animal testing by promoting human-relevant safety assessments across diverse applications, including cosmetics, pharmaceuticals, and environmental chemicals. Among these methodologies, computational models like quantitative systems toxicology (QST) have emerged as powerful tools, enabling the simulation of mechanisms underlying drug (or chemical) induced toxicity to predict potential adverse outcomes. Valproic acid (VPA), a treatment for epilepsy, convulsions and bipolar disorder, is associated with a risk of drug-induced liver injury. The mechanism of hepatotoxicity is not fully understood, although VPA’s competitive inhibition of fatty acid metabolism via carnitine palmitoyl transferase 1 (CPT1) in the liver is a leading hypothesis. In this study, we employed a QST approach by integrating a human physiologically-based pharmacokinetic model of VPA with the large-scale liver metabolism model HEPATOKIN1 to evaluate whether simulated VPA dosing with increasing CPT1 inhibition predicted relevant clinical markers for hepatotoxicity. The integrated model predicted a dose-dependent increase in hepatic triaclyglyceride as a result of the competitive inhibition of CPT1 by VPA, consistent with clinical observations. Notably, explicitly including PPARα-mediated regulatory effects on key liver enzymes was essential to ensure biologically consistent outcomes in liver metabolism. These results highlight the necessity of including relevant regulatory pathways in QST applications to achieve credible and physiologically relevant safety predictions.
2026-03-21 | MODEL2509090001 | BioModels
Project description:Hepatic ischemia-reperfusion (I/R) has long affected the success rate of liver transplant. Though zone-specific injury induced by I/R was observed, elaborated cellular and molecular mechanisms underlying the I/R injury pattern have not been revealed. Spatial transcriptomics analysis has great potential to uncover the mechanisms of liver I/R injury.
2023-02-07 | GSE217936 | GEO
Project description:The liver is the only organ with the ability to regenerate following surgical or toxicant insults, and partial hepatectomy (PH) serves as an experimental model of liver regeneration (LR). Dynamic changes in gene expression occur from the periportal to pericentral regions of the liver following PH; thus, spatial transcriptomics, combined with a novel computational pipeline (ADViSOR [Analytic Dynamic Visual Spatial Omics Representation]), were employed to gain insights into the spatiotemporal molecular underpinnings of LR. ADViSOR, comprised of time-interval principal component analysis (TI-PCA) and sliding dynamic hypergraphs (sDyHyp), was applied to spatial transcriptomics data on 100 genes assayed serially through LR, including key components of the Wnt/beta-catenin pathway at critical time points after PH. This computational pipeline identified key functional modules demonstrating cell signaling and cell-cell interactions, inferring shared regulatory mechanisms. Specifically, ADViSOR analysis suggested that macrophage-mediated inflammation is a critical component of early LR and confirmed prior studies showing that Ccnd1, a hepatocyte proliferative gene, is regulated by the Wnt/ß-catenin pathway. These findings were subsequently validated through protein localization which provided further confirmation and novel insights into the spatiotemporal changes in the Wnt/beta-catenin pathway during LR. Thus, ADViSOR may yield novel insights in other complex, spatiotemporal contexts.
2023-09-28 | GSE244211 | GEO
Project description:Demonstration of reduced biological effects with a prototypic modified risk tobacco product. Towards a systems toxicology-based risk assessment, we investigated molecular perturbations accompanying histopathological changes in a 28-day rat inhalation study combining transcriptomics with classical histopathology, and demonstrated reduced biological activity of a prototypic modified risk tobacco product (pMRTP) in comparison to the reference research cigarette 3R4F. Rats were exposed to filtered air or to three concentrations of mainstream smoke (MS) from 3R4F, or to a high concentration of MS from a pMRTP. Histopathology revealed dose-dependent changes for 3R4F: irritative stress-related in nasal and bronchial epithelium and inflammation-related in the lung parenchyma. For pMRTP, significant changes were seen in the nasal epithelium only. Transcriptomics data were obtained from nasal and bronchial epithelium and lung parenchyma. Dose-dependent gene expression changes were seen for 3R4F with much smaller changes for pMRTP. A computational-modeling approach that is based on causal models of tissue-specific biological networks identified cell stress, inflammation, cell proliferation, and senescence as the most perturbed molecular mechanisms. These perturbations correlated with the histopathological observations. Only weak perturbations were observed for the pMRTP. In conclusion, a correlative evaluation of classical histopathology together with gene expression?based computational network models may facilitate a systems toxicology-based risk assessment as shown for a pMRTP.
2014-05-15 | GSE50254 | GEO